Antigen recognition by γδ T cells

gamma delta T cells contribute to host immune competence uniquely. This is most likely because they have distinctive antigen-recognition properties. While the basic organization of gamma delta T-cell receptor (TCR) loci is similar to that of alpha beta TCR loci, there is a striking difference in how the diversity of gamma delta TCRs is generated. gamma delta and alpha beta T cells have different antigen-recognition requirements and almost certainly recognize a different set of antigens. While it is unclear what most gamma delta T cells recognize, the non-classical major histocompatibility complex class I molecules T10 and T22 were found to be the natural ligands for a sizable population (0.2-2%) of murine gamma delta T cells. The recognition of T10/T22 may be a way by which gamma delta T cells regulate cells of the immune system, and this system has been used to determine the antigen-recognition determinants of gamma delta T cells. T10/T22-specific gamma delta T cells have TCRs that are diverse in both V gene usage and CDR3 sequences. Their V gamma usage reflects their tissue origin, and their antigen specificity is conferred by a motif in the TCR delta chain that is encoded by V and D segments and by P-nucleotide addition. Sequence variations around this motif modulate affinities between TCRs and T10/T22. That this CDR3 motif is important in antigen recognition is confirmed by the crystal structure of a gamma delta TCR bound to its ligand. The significance of these observations is discussed in the context of gamma delta T-cell biology.